Regulation of the anti-Sm autoantibody response in systemic lupus erythematosus mice by monoclonal anti-Sm antibodies.
The administration of certain monoclonal anti-Sm antibodies (2G7, 7.13) induced most MRL/lpr mice to become anti-Sm positive by 5 mo of age, although other anti-Sm monoclonals (Y2, Y12) suppressed the spontaneous response. Positive anti-Sm antibody enhancement occurred efficiently only in MRL/lpr mice and not in other systemic lupus erythematosus mice that have little spontaneous anti-Sm production. The enhancement by anti-Sm antibodies was specific for the anti-Sm response. The mechanism of the passive antibody enhancement was apparently not isotype- or idiotype-related. The fine specificity of the anti-Sm monoclonal antibody may be essential to its enhancing or suppressing effects, since both enhancing monoclonals recognized only the D Sm polypeptide, whereas both suppressing monoclonals saw the D and the B polypeptides. Furthermore, analysis of serial bleeds from unmanipulated MRL mice that developed anti-Sm positivity showed that the D specificity almost always appeared first. We hypothesize, therefore, that those animals in which an anti-Sm response is initiated by D-specific B-cell clones can become serologically positive with the aid of a positive feedback loop. In contrast, animals in which the initial specificity is for both B and D peptides would be prevented from developing a full anti-Sm response.
Eisenberg
R A
RA
Department of Medicine, University of North Carolina, Chapel Hill 27599.
Pisetsky
D S
DS
Craven
S Y
SY
Grudier
J P
JP
O'Donnell
M A
MA
Cohen
P L
PL
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000276:immunology; D000917:Antibody Formation; D001323:Autoantibodies / Q000032:analysis / Q000096:biosynthesis*; D015415:Biomarkers / Q000032:analysis; D004195:Disease Models, Animal; D015151:Immunoblotting; D007130:Immunoglobulin Idiotypes / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008815:Mice, Inbred Strains; D013045:Species Specificity
D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D015415:Biomarkers; D007130:Immunoglobulin Idiotypes